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Synthesis 2010(14): 2319-2344  
DOI: 10.1055/s-0029-1220013
REVIEW
© Georg Thieme Verlag Stuttgart ˙ New York

Practical Methods for the Synthesis of Symmetrically α,α-Disubstituted α-Amino Acids

Vadim A. Soloshonok*a, Alexander E. Sorochinskyb
a Department of Chemistry and Biochemistry, The University of Oklahoma, Room 208, 620 Parrington Oval, Norman, OK 73019-3051, USA
Fax: +1(405)3256111; e-Mail: vadim@ou.edu;
b Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of the Ukraine, Murmanska Street 1, Kyiv-94 02660, Ukraine
Further Information

Publication History

Received 29 March 2010
Publication Date:
18 May 2010 (online)

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Abstract

This report provides an overview of the practical methods for preparing symmetrically α,α-disubstituted α-amino acids and their derivatives. Despite the growing application of this particular type of sterically constrained α-amino acid in the de novo design of peptides and peptidomimetics, synthetically important achievements in the field have not been summarized so far. Classical methods, such as the Bucherer-Bergs and Strecker reactions of sym-dialkyl and cyclic ketones, as well as recent methods involving dialkylation of nucleophilic glycine equivalents and Ugi reactions, are presented.

1 Introduction

2 Bucherer-Bergs and Strecker Reactions of sym-Dialkyl and Cyclic Ketones

3 Dialkylation of Schiff Bases Derived from Glycine Esters

4 Dialkylation of Ethyl Isocyanoacetate

5 Dialkylation of Ethyl Nitroacetate

6 Ugi Reaction

7 Conclusions

Key words

sterically constrained - α,α-disubstituted α-amino ­acids - dialkylation - nucleophilic glycine equivalents - nickel(II) complexes